1. Field of the Invention
The invention relates to the generation of singlet oxygen, and more particularly, to methods and systems to increase the triplet yields of photosensitizers, by coupling to surface plasmons, which invariably results in more singlet oxygen generation.
2. Related Art
Molecular oxygen has a unique electronic configuration characterized by a partially filled set of antibonding π* orbitals. As predicted by Hund's rule, the lowest energy state of the molecular oxygen has maximum multiplicity, i.e. is a triplet ground state. Molecules whose outermost pair of electrons have parallel spins (symbolized by ↑↑) are in the “triplet” state; molecules whose outermost pair of electrons have antiparallel spins (symbolized by ↑↓) are in the “singlet” state. Ground-state oxygen is in the triplet state indicated by the superscripted “3” in 3O2, —its two unpaired electrons have parallel spins, a characteristic that, according to rules of physical chemistry, does not allow them to react with most molecules. Thus, ground-state or triplet oxygen is not very reactive. However, triplet oxygen can be activated by the addition of energy, and transformed into reactive oxygen species 1O2 having a lifetime of approximately 45 minutes.
If triplet oxygen absorbs sufficient energy to reverse the spin of one of its unpaired electrons, it forms the singlet state. Singlet oxygen, abbreviated 1O2*, has a pair of electrons with opposite spins; though not a free radical it is still highly reactive. (The * symbol is used to indicate that this is an excited state with excess energy)

The physical, chemical and biological properties of singlet oxygen attracted serious attention from researchers during the 1960's despite its discovery in 1924. Since singlet oxygen can readily react with many biological targets and destroy a wide variety of cells, the photosensitized production of singlet oxygen has significance in a range of areas, especially in photodynamic therapy (PDT).
Photodynamic therapy (PDT) has been widely used in both oncological, (e.g. tumors and dysplasias) and nononcological (e.g. age-related macular degeneration, localized infection and non-malignant skin conditions) applications.(1-4) PDT is applied in multiple steps for the treatment of patients with cancer. Three primary components are involved in PDT: light, a photosensitizing drug and oxygen. In the first step, a photosensitizing agent is deposited on/or near surface tumors after its injection into the bloodstream. Then, the photosensitizer-deposited cancer tumor is exposed to light. Here, the excited photosensitizer transfers its energy to molecular oxygen while returning to the ground state, which results in the production of singlet oxygen. Subsequently, singlet oxygen destroys nearby cancer cells.(1) The singlet oxygen is a cytotoxic agent and reacts rapidly with cellular components to cause damage that ultimately leads to cell death and tumor destruction.(4) PDT treatments are only effective within a specific range of singlet oxygen supply.(5)
Triplet oxygen can also be activated by the addition of energy, in the form of a single electron to form a triplet oxygen called superoxide, abbreviated O2.−.3O2+e−→O2.−
Superoxide is a radical that is a precursor to other oxidizing agents, including singlet oxygen. Superoxide can react with the hydroxyl radical (HO.) to form singlet oxygen (1O2*), as shown below:O2.−+HO.→1O2*+HO−
Currently, the intensity of light is commonly adjusted to control the extent of singlet oxygen generation, but there are some limitations to this method. High fluency rates of the exposure light will lead to oxygen depletion and photosensitizer photo-bleaching.(3) However, low fluency rates of exposure light, lends to a long exposure time and can cause vascular shutdown, a precursory condition to hypoxia in the tissue.(5,7) One notable approach to control the fluency rate of exposure light is called interstitial PDT, where precise amount of light is delivered locally to tumors through inserted optical fibers.(8) The interstitial PDT also allows the real-time monitoring of the progression of the treatment via online collection of assessment parameters through the optical fibers.(8) It is important to note that despite the better control over fluency rate the photobleaching of the photosensitizers remains an issue.
Since singlet oxygen plays a very important role in cell damage, an abundant supply of oxygen is required. However, photodynamic therapy is currently limited by the insufficient generation of singlet oxygen while reacting with biological targets and photobleaching of the photosensitizers remains an issue. Thus, it would be advantageous to provide a method to resolve these problems by increasing singlet oxygen generation and reduce photobleaching of the photosensitizer.